The present invention relates to cartridges such as ion exchange cartridges or adsorption cartridges which are useful, for instance, in dialysis. In particular, the present invention relates in general to the regeneration or purification of used dialysate fluids. The present invention further relates to methods of conducting dialysis using certain cartridges.
Dialysis is a treatment that removes the waste products and excess fluid that accumulate in the blood as a result of kidney failure. Chronic renal failure is when the renal function has deteriorated to about 25% of normal. This amount of deterioration causes significant changes in the blood chemistry and is about the time that people feel poorly enough that they seek medical care. If medical treatment is sought at that time, progression can be slowed. Late stage chronic renal failure is when kidney function has decreased to 15%. End stage renal failure is when kidney function is at 5% of normal. Death will most likely result without treatment at this point. There are approximately as many patients yearly who experience acute renal failure as with chronic renal failure, approximately ½ of these acute patients need medical treatment. On the whole, acute patients are more ill and less stable than chronic patients. They are frequently treated in ICU or CCU units of a hospital and cannot be moved. Acute patients may not survive, or may recover kidney function, or may become chronic dialysis patients. There is no current cure for renal disease. However, one treatment is transplantation, which is where a human kidney is surgically placed in the body and connected to the bladder. Daily medication is needed to keep the body from rejecting the transplanted kidney. Also, there is peritoneal dialysis (PD). With this treatment, a mild saltwater solution containing dextrose and electrolytes called dialysate is put into the peritoneal cavity. Because there is a rich blood supply to this abdominal cavity, urea and other toxins from the blood and fluid are moved into the dialysate, thereby cleaning the blood. The dialysate is then drained from the peritoneum. Later “fresh” dialysate is again put into the peritoneum.
Also, there is hemodialysis. This is a method of blood purification in which blood is continually removed from the body during a treatment session and passed through a dialyzer (artificial kidney) where metabolic waste and excess water are removed and pH and acid/base balances are normalized. The blood is simultaneously returned to the body. The dialyzer is a small disposable device consisting of a semi-permeable membrane. The membrane allows the wastes, electrolytes, and water to cross but restricts the passage of large molecular weight proteins and blood cells. Blood is pumped across one side of the membrane as dialysate is pumped in the opposite direction across the other side of the membrane. The dialysate is highly purified water with salts and electrolytes added. The machine is a control unit which acts to pump and control pressures, temperatures, and electrolyte concentrations of the blood and the dialysate. The average length of one hemodialysis treatment is 3-5 hours.
There are several types of hemodialysis:
a) Single Pass—hemodialysis is the most common treatment for renal disease. Most hemodialysis treatments are performed with single pass dialysis machines. They are called single pass because the dialysate (cleaning solution) passes by the blood in the dialyzer one time and then is disposed. Single pass dialysis machines generally require:                1) a water source capable of delivering at least 1000-1500 ml/min (assuming a 50% rejection rate by the R.O. system)        2) a water purification system sufficient of providing a continuous flow of 500-800 ml/min of purified water.        3) an electrical circuit of at least 15 amps in order to pump and heat 500-800 ml of water/min.        4) a floor drain or any other receptacle capable of accommodating at least 500 ml of used dialysate/minute as well as the rejected water from the R.O. system.        
b) Sorbent Dialysis—does not require a continuous water source, a separate water purification machine or a floor drain because it continuously regenerates a small volume of dialysate and incorporates a water treatment system within the machine. Therefore, sorbent systems are truly portable.                1) sorbent systems require only a 5 amp electrical source because they recycle the same small volume of dialysate throughout the dialysis procedure. The heavy duty dialysate pumps and heaters used for large volumes of dialysate in single pass dialysis are not needed.        2) the sorbent system can use 6-12 liters of tap water from which dialysate is made for an entire treatment.        3) the sorbent system uses a sorbent cartridge—which acts both as a water purifier and as a means to regenerate used dialysate into fresh dialysate. The infusate system acts with it to properly balance the electrolyte composition of the regenerated dialysate.        
The sorbent cartridge containing zirconium phosphate (ZrP) and hydrous zirconium oxide (HZO) ion-exchange materials has been historically used for the REDY regeneration hemodialysis system. The scheme of the REDY cartridge is shown in FIG. 1. The sorbent cartridge is shown with the inlet and the outlet identified as numeral 11 and numeral 13, respectively. FIG. 2 shows various functions of each layer in a REDY cartridge.
The principle of the REDY cartridge is based on the hydrolysis of urea to ammonium carbonate by the enzymatic reaction of urease. The following equation shows a reaction for urea conversion to ammonia in the presence of urease:
The ammonia and ammonium ions are then removed by the zirconium phosphate in exchange for the hydrogen ions and Na+ ions, which are counter-ions in the cation exchanger. Zirconium phosphate also serves as cation exchanger to remove Ca, Mg, K, and all toxic metals in dialysate, thus allowing a balance of electrolyte level in the patient's blood (Ca, Mg, K) to be maintained by using an infusate system, as well as providing safety for dialysis treatment with regard to water quality. The carbonate from the urea hydrolysis then combines with the hydrogen ions in zirconium phosphate to form bicarbonate, which is delivered to the uremic patient as a base to correct for acidosis. Zirconium phosphate can be represented as inorganic cation exchange material with the molecular structure as shown below:
As shown, the material contains both H+ and Na+ as counter-ions, which are responsible for ion exchange. The relative content of these ions can be controlled by the pH to which acid ZrP (or H+ZrP) is titrated with NaOH. The composition of the resultant product of titration, Nax+H2−x+ZrP (or abbreviated as “NaHZrP” herein), may vary during ion exchange processes in dialysate. The hydrous zirconium oxide (HZO) containing acetate (HZO.Ac) as a counter ion serves as an anion exchanger to remove phosphate. The material also prevents leaching of phosphate from NaHZrP and removes toxic anions (e.g., fluoride) in water that may cause harm to a patient during dialysis. The acetate released during ion exchange is also a base to correct for acidosis by acetate metabolism. The compositional formula of hydrous zirconium oxide (HZO) can be ZrO2.nH2O (i.e. zirconium oxide hydrate) or ZrO2.nOH . . . H+An− in the anion form wherein An is an anion attached to HZO, such as acetate (“Ac”), chloride, etc. Without the anion, it can be considered as partially oxalated zirconium hydroxide with various degrees of O2−, OH− and H2O bonded to Zr, i.e., Zr(OH)xOy(H2O)z. The granular activated carbon in the cartridge is used in the REDY cartridge for the removal of creatinine, uric acid, and nitrogenous metabolic waste of the patient as well as chlorine and chloramine from water. Thus the REDY regenerative dialysis system is efficient to provide both safety and simplicity of water treatment and hence convenience for hemodialysis. The efficacy and safety record of the system has been well established. Nevertheless, there have been significant technological advancements in dialysis treatments as a whole, and thus, a new and improved cartridge is required to meet the needs of today's dialysis systems.
Sorbent cartridge designs would be preferred that can further reduce or prevent release of organic impurities, sodium, zirconium ions such as from zirconium phosphates, acetate ions such as from HZO.Ac, and the like, from components of a sorbent cartridge to dialysate. Accordingly, in the area of dialysis, it would be beneficial to overcome one or more of the above-described disadvantages.